A member of the ETVPEA3 subfamily of Ets transcription factors, ETV4 is necessary for anchorage-independent growth of prostate cancer cells and regulates the epithelial-to-mesenchymal transition. Additionally, a recent studydemonstrated that activation of ETV4 is occurs alongside activation of Ras and PI3K pathways in metastaticprostate cancer and, importantly, that genetic ablation of ETV4 significant decreases metastasis. Synthetic modulators that perturb ETV4 function have high value as mechanistic probes to dissect the role of this protein in primary tumor growth and the transition to metastatic phenotypes, for which there is conflicting data. The underlying hypothesis for this project is that a small molecule that blocks the ability of ETV4 to function as a transcriptional regulator will correspondingly inhibit key invasion pathways necessary for prostate cancer metastasis. We successfully leveraged our expertise in this area to discover the first inhibitors of ETV4 by targeting a key binding partner, the coactivator Med25.